Glycosylated Haemoglobin

These laboratory tests are used to assess control in diabetes mellitus.

Chromatography of normal adult blood divides into two parts:

• HbA (HbA0) 92-94%
• HbA1 (6-8%) where the B chain has an additional glucose group

HbA1 itself consists of three different glycosylations, the HbA1c subgroup being the most useful, usually measured by isoelectric focusing or electrophoresis.

The glycosylation of haemoglobin occurs at a variable (non-linear rate) over time, during the whole lifespan of the red blood cell (RBC) (normally 120 days). This means the relative proportion of glycosylated haemoglobin at any one time depends on the mean glucose level over the last 120 days.

Normal levels (laboratory normal "range") will differ depending on whether HbA1 or HbA1c is measured, and the method used - use your lab's reference range (EDTA (FBC) bottle).¹

Glycosylated haemoglobin (HbA1c) is usually a reliable indicator of diabetic control except in the following situations:

• Where the average RBC lifespan is significantly less than 120 days - such will usually give rise to low HbA1c results as 50% of glycosylation occurs in days 90-120.² Common causes:¹
  • Increased red cell turnover: blood loss, haemolysis, haemoglobinopathies and red cell disorders, myelodysplastic disease
  • Interference with test (depends on method used: persistent fetal haemoglobin and haemoglobin variants, carbamylated haemoglobin (uraemic patients)
• In patients who fluctuate between very high and very low levels - glycosylated haemoglobin readings can be misleading (clinician should compare with extra information obtained from home capillary blood glucose tests).
• HbA1c can be very useful in identifying patients who may be presenting an unrealistically good report of their home glucose tests.

HbA1c results in the UK have usually been aligned to the assay used in the Diabetes Control and Complications Trial (DCCT), expressed as a percentage (DCCT-HbA1c) - non-diabetic "normal" range being 4-6%. From 1st June 2009 HbA1c results in the UK are standardised to the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) which will allow global comparison of results, with the equivalent normal non-diabetic range of IFCC-HbA1c being 20-42 mmol/mol.³

• The general DCCT suggested an HbA1c target of < 7.5% (59 mmol/mol) (ideally < 6.5%-7.0% = 48-53 mmol/mol) for the management of diabetic patients, which should be individualised and agreed with the patient (considering co-morbidity, life expectancy, hypoglycaemia frequency, etc.).⁴
• Do not test more frequently than every 3 months - and avoid over-interpreting results. Look for trends rather than the difference in two consecutive results - test imprecision varies with method used and is typically 3-4%.
• HbA1c is not a diagnostic test for diabetes, nor should it be used to screen for diabetes.
• Mean plasma glucose results are 10-15% higher than the equivalent HbA1c.⁵

Fructosamine is the glycosylated fraction of all plasma proteins (predominantly albumin), but considered less accurate because of the numerous factors affecting the half-lives of the many components. It generally reflects average glucose in the previous two weeks. If available it may be used where there is reduced red cell survival time.